Microfluidic applications generally seek to control fluids, reagents, and objects at the microscale. The development of individual components to either mimic traditional processes or to realize novel processes remains important to development in the field.
Chemical production, sample analyses, and chemical research have historically been based on laboratory-scale or plant-scale systems. In the early 1990s, microfabrication methods were borrowed from the microelectronics industry to create small channels that could serve as tiny chemical reactors or laboratories. This new approach spawned the field of microfluidics, which has become associated with all means of controlling fluid and its contents at the microscale. The ability to replicate traditional systems at the microscale remains an important goal. On the other hand, the small length scale also allows creation of novel systems. Recent developments in microfluidics have demonstrated sub-millimeter microreactors for chemical production and microscale analytical systems, as well as systems for direct manipulation of cells. Much current effort is spent demonstrating and developing individual components for controlling fluids, reagents, and objects at the microscale, either to mimic traditional processes or to realize new processes.
The small length scale of microfluidic devices has important consequences for flow, transport, and reaction. While it is intuitive that objects in a fluid stream will move in the direction of flow, other fluid-dynamic forces generated by velocity gradients in a flow field are known to move objects across streamlines. For example, the well-known “tubular pinch effect” describes the movement of blood cells to specific annular positions within blood vessels, and inertial migration in channel flow has been exploited to concentrate cells and to perform size-based particle and cell separations.
Recirculating flows in microfluidic systems offer a fundamentally different means of controlling fluids, reagents, and objects. In some flows, small laminar eddies form that can perform the final mixing of reagents so important for chemical reactions, and the extent of mixing in these eddies can affect many performance parameters, such as yield and selectivity. Such eddies are also known to affect other related parameters, such as sedimentation and entrainment of small objects. For example, small laminar eddies formed in turbulence have been implicated in plankton blooms due to the differential effect on predator and the blooming prey.
It is known that oscillating a fluid, for example, at audible frequencies, can generate a streaming flow within the fluid, even in the absence of a net flow. Two distinct types of streaming flows are known high-intensity streaming and low-intensity streaming. These two types of streaming flows result from different physical mechanisms. High-intensity steady streaming is driven by body forces generated throughout the fluid (e.g., “quartz wind”) and is a nonconservative effect resulting from the absorption of acoustic energy by the fluid, which may cause significant heat generation. Low-intensity steady streaming, by contrast, is a conservative effect driven locally from within boundary layers, and typically involves fluid recirculation. The term acoustic streaming is often used to describe both types of streaming, but steady streaming is a more appropriate term for low-intensity streaming.
Low-intensity steady streaming provides a method for creating eddies in a fluid. The characteristics of the recirculating eddies, such as the eddy strength, size, and location, can be predictably achieved by the appropriate selection of geometry, oscillation parameters and fluid properties. Recirculating eddies generated by low-intensity steady streaming are distinctly different from flow patterns in typical microfluidic devices, leading to fundamentally different reagent mixing and a unique ability to trap microscopic objects at fixed locations. The present invention focuses on the use of low-intensity steady streaming to produce small eddies that can be utilized, for example, as relatively simple and gentle traps for small objects, including motile cells.
In particular, the present invention is directed to generating low-intensity streaming flows in a microfluidic channel or chamber to create eddies, and utilizing the properties of such microfluidic flow streams for controlling fluids, reagents, and objects at the microscale. For example, it is often desirable to study single cells in an environment that is compatible with the cell and without damaging or otherwise modifying the cell. Similarly, it may be desirable to trap specific cells or other particles for purposes of either concentrating or filtering such particles from a fluid.
Conventional methods for trapping single cells include, for example, optical tweezers or laser traps that utilize focused laser radiation to manipulate the cells. Such systems, however, have several drawbacks. For example, conventional trapping systems may produce undesirably high forces and/or thermal stresses on the cell and may not be suitable for cells that are light- and/or heat-sensitive. Another method utilizes dielectrophoretic traps that apply an electric field to create trapping forces. Such systems, however, generally polarize the cell membrane and may therefore alter the behavior of the cell. Moreover, such trapping systems must typically be designed to target a specific cell and cell medium, and are not easily modified to target a different cell.
There remains a need, therefore, for improved methods of trapping particles and/or cells from a fluid medium.